Agonists and antagonists are two types of opioid drugs used in opioid dependence treatment with drastically different mechanisms of action. Upon binding to opioid receptors, agonist drugs activate them, triggering a biological response.
Although antagonists also act on the same receptors, they do so without activating them and inhibit the effects of agonists.
This article will provide an in-depth comparison of agonist vs. antagonist drugs, explaining how they work, what side effects they produce, and more.
What Is an Agonist?
An agonist is a natural or artificial chemical that binds to specific receptors in the central nervous system (CNS) and produces a biological response by activating them. Natural agonists include neurotransmitters and hormones, such as serotonin or endorphin. Artificial agonists, meanwhile, are drugs created to resemble natural agonists.
For example, endorphins are natural agonists known as the body’s natural painkillers, as they bind to opioid receptors, reducing the perception of pain. Meanwhile, opioid pain medications like oxycodone are artificial agonists created to mimic the effects of endorphins; they relieve pain by binding to the same receptors as endorphins.
Moreover, opioid agonists can lead to dependence and addiction, as repeated exposure to them alters brain chemistry. Specifically, it causes the brain to decrease the production of natural endorphins while increasing that of opioid receptors, leading to tolerance and dependence.
3 Main Types of Agonists
The three main types of agonists are as follows:
- Full agonists. These activate receptors to the fullest extent, producing an intense biological response. Some examples of full opioid agonists include heroin, morphine, and methadone. Even though the latter can be used to treat opioid dependence, researchers from the Addiction Research Center found that its effects are virtually indistinguishable from those of morphine and heroin.
- Partial agonists. This agonist type binds to receptors without activating them fully, thus producing a weaker response. Some examples include varenicline, a medication used to help people stop smoking, and buprenorphine, an opioid most commonly used to treat opioid dependence. Although it can also be used for pain relief, buprenorphine’s effects plateau at a certain dose, which is why it is thought to have a lower potential for abuse. Nonetheless, you can get addicted to it.
- Inverse agonists. Although inverse agonists attach to the same receptors as full agonists, they produce the opposite response. For example, H-1 antihistamines like cetirizine produce an effect on receptors that is opposite to histamine, alleviating allergy symptoms.
Moreover, researchers from the University of Arkansas for Medical Sciences found that chronic exposure to μ- and δ-opioid agonists may convert opioid antagonists like naloxone into inverse agonists at these receptors. The findings suggest that this may have implications for tolerance and dependence.
On that note, let’s clarify the definition of antagonists.
What Is an Antagonist?
An antagonist is a chemical substance that binds to receptors without activating them. Instead, it blocks, reverses, or inhibits the effects of agonists.
Some examples of antagonist drugs include:
- Beta-blockers like propranolol
- Opioid antagonists, such as naloxone
- Dopamine antagonists (e.g., droperidol)
For example, naloxone (Narcan®) is used to reverse an opioid overdose. If you take an excessive amount of opioids, a timely administration of naloxone can save your life. This is because naloxone binds to opioid receptors with greater intensity than opioid agonists like heroin, thereby dislodging them and preventing them from binding to these receptors.
Since naloxone occupies opioid receptors but doesn’t activate them, it reverses respiratory depression and other life-threatening effects of an opioid overdose.
Types of Antagonists
Here are the main types of antagonists:
- Competitive antagonists. Competitive antagonists like naloxone and naltrexone prevent agonists from binding to the receptor by competing with them for the same binding site. However, increasing the concentration of agonists can suppress their effects.
- Non-competitive antagonists. These bind to a different site of the receptor than agonists, altering its shape and preventing agonists from binding to the receptor. Unlike competitive antagonists, non-competitive antagonists like ketamine cannot be overcome by increasing agonist concentration.
- Irreversible antagonists. These bind to receptors tightly, forming a covalent bond that cannot be easily broken and permanently altering the receptor’s ability to function. Irreversible antagonists, such as phenoxybenzamine, cannot be washed out or displaced.
Now that we’ve cleared up the definition of agonist vs. antagonist, let’s discuss the key differences between them in regard to opioid use disorder (OUD) and its treatment.
Agonist vs. Antagonist: Key Differences in OUD
The key difference between agonists and antagonists is that agonists produce the typical effects associated with opioid medications, such as euphoria, pain relief, and sedation. Therefore, they have a high potential to cause OUD, also known as opioid addiction. Antagonists, meanwhile, block these rewarding effects and, therefore, don’t have addictive properties.
With this in mind, let’s compare agonists vs. antagonists in terms of their mechanisms of action, side effects, and impact on OUD.
How They Work
Opioid agonists and antagonists work in the opposite way, even though they interact with the same receptors.
Agonists bind to opioid receptors and activate them fully (full opioid agonists) or partially (partial opioid agonists). While full opioid agonists trigger strong analgesic, sedating, and euphoric effects, partial opioid agonists, too, can cause these responses, albeit to a lesser extent.
By contrast, opioid antagonists attach to opioid receptors, but they don’t activate them. Instead, they prevent opioid agonists from binding to and activating these receptors, inhibiting their effects.
Side Effects
Opioid agonists and antagonists often cause similar side effects. However, constipation, sedation, and respiratory depression are common with agonists, whereas antagonists are more likely to cause precipitated withdrawal symptoms due to poorly timed and managed administration. However, these can also occur with buprenorphine, a partial agonist.
Moreover, opioid agonists can cause a life-threatening overdose, whereas antagonists—namely, naloxone—are used to treat it.
Both opioid agonists and antagonists may cause:
- Fatigue
- Nausea
- Vomiting
- Dizziness
- Headache
- Stomach ache
- Sleep disturbances
Naloxone nasal spray can also cause nasal dryness, congestion, and inflammation, whereas agonist and antagonist injections can cause injection site reactions like redness and swelling. Injecting any of these substances may also expose you to a risk of bloodborne diseases, such as hepatitis B, hepatitis C, and HIV.
Inform your doctor about any side effects you experience while taking agonist or antagonist medications, including those not listed above.
Impact on OUD
Both opioid agonists and antagonists can be used to treat OUD, usually in medication-assisted treatment (MAT).
Two agonists—methadone and buprenorphine—are FDA-approved for the treatment of OUD. These replacement opioids are meant to curb cravings and opioid withdrawal symptoms.
Buprenorphine/naloxone (Suboxone®) is generally considered a safer alternative to pure buprenorphine due to naloxone, which decreases the risk of opioid abuse. On its own, naloxone is only used to reverse an opioid overdose.
Now that we’ve compared agonist vs. antagonist medications, let’s clear up some common misconceptions about them.
Common Misconceptions About Agonists and Antagonists
The most common misconception about opioid agonists and antagonists is that replacing other opioids with them cures opioid use disorder
In reality, people who opt for treatments involving agonists end up swapping one addiction for another rather than recovering.
Contrary to popular belief, methadone and buprenorphine are addictive. The fact that they are used in opioid addiction treatment doesn’t mean they are safe; they can produce opioid-like effects, especially when abused (i.e., taken in large doses, crushed and injected, etc.).
Meanwhile, antagonists like naltrexone are only effective under specific circumstances, i.e., when used as part of a comprehensive opioid dependence treatment.
Traditional treatments like MAT (medication-assisted treatment) use opioid agonists or antagonists as substitutes for more potent and dangerous opioids, but they do not fix the neurochemical imbalance resulting from opioid exposure. Since such treatments fail to address the root cause of opioid dependence, they can—and more often than not—lead to relapse, exposing patients to the risk of overdose and death.
Another misconception is that if you quit opioids, you’ll have to rely on opioid agonists or antagonists for months, years, and even decades. This couldn’t be further from the truth; if you choose a treatment that tackles opioid dependence at its root, you will be able to resume an opioid-free life right after completing the treatment.
How ANR Treatment Uses Antagonists & Anesthesia to Support Lasting Recovery
Accelerated Neuro-Regulation (ANR) is a revolutionary opioid dependence treatment that facilitates lifelong recovery by re-regulating the endorphin-receptor system and achieving a neurochemical balance.
ANR stands out as the first and only treatment that targets the very root of opioid dependence. It works by re-regulating the endorphin-receptor system with the help of naltrexone and other medications that cleanse and block opioid receptors. At the same time, ANR allows the body to resume normal endorphin production.
The treatment is performed under sedation in an ICU setting of accredited hospitals by a team of healthcare professionals, including critical care physicians and anesthesiologists. ANR patients experience no discomfort of going through active withdrawals and wake up with a rebalanced nervous system without cravings or other withdrawal symptoms.
Unlike traditional methods, the ANR treatment doesn’t involve any potentially addictive opioid agonist medications, as these simply aren’t needed. Once you’re done with the treatment, you can leave opioids in the past and forget about the fear of relapse.
To learn more about ANR, contact us today for a free consultation!
Key Takeaways
When it comes to agonists vs. antagonists for OUD treatment, antagonists are a significantly safer option since they don’t cause euphoric effects or dependence.
However, naltrexone is only effective when used in a comprehensive treatment program designed to target the root of opioid dependence and restore normal brain function.
Let’s summarize what we covered today:
- Agonists are chemicals that produce a biological response by binding to and activating certain receptors in the brain.
- Antagonists are chemicals that prevent agonists from interacting with specific receptors or suppress their effects by binding to specific receptors.
- Contrary to popular belief, it is possible to lead an opioid-free life, regardless of how long you’ve been dependent on opioids; the key is to opt for a treatment that targets the deep-rooted causes of opioid dependence rather than its symptoms.
Agonist vs. Antagonist FAQ
Naltrexone (Vivitrol®) is an antagonist commonly used in opioid dependency treatment. It blocks the euphoric effects of opioids, reducing the risk of relapse and opioid misuse. However, naltrexone is only effective when used in a comprehensive treatment program designed to target the root of opioid dependence and restore normal brain function.
You can become dependent on agonist medications like methadone or buprenorphine. Whether you take them for pain relief or OUD treatment, they have the same effects on the brain as other opioids.
Switching from an agonist treatment to an antagonist treatment is only safe under medical supervision. If you want to switch from an agonist—methadone or buprenorphine—to an antagonist, talk to your doctor. Never make any changes to your treatment without consulting your doctor.
Agonist and antagonist medications aren’t normally used together, as they have opposite effects; antagonists counteract the effects of agonists. Using these medications together also increases the risk of precipitated withdrawal symptoms.
